Background/Purpose: To determine the effect of RORγt overexpression in T cells on the development of collagen induced arthritis (CIA).

Methods: Arthritis was induced with chicken type II collagen (CII) in both C57BL/6 (B6) and CD2 T cell-specific RORγt Transgenic (RORγt Tg) mice.  Anti-CII antibody in sera was measured by ELISA. At 10 days after the first immunization of CII, lymph node (LN) cells were cultured with or without CII, and then the expression level of cytokine, transcription factor and chemokine receptor on CD4⁺ T cells were analyzed by flow cytometer and RT-PCR.  Cytokine levels in culture supernatants were measured by ELISA. Joint infiltrating cells were also examined by flow cytometer. Cytokine production and suppressive function of Foxp3⁺ regulatory T cells was analyzed in vitro. Total draining lymph nodes cells or CD4⁺cells were harvested from B6 mice or RORγt Tg mice at 10 days after the first immunization of CII, and cells were injected into B6 mice intravenously at 10 days after the immunization of CII.  Mice were also immunized with CII in CFA intradermally on 11 days after the cell transfer.

Results: CIA was significantly suppressed in RORγt Tg mice compared with B6 mice. Anti-CII antibody in sera was also reduced in RORγt Tg mice. RORγt expression and IL-17 production in CII reactive CD4⁺ T cells was significantly increased in RORγt Tg mice. Although there was no difference in IFNγ production and T-bet and Foxp3 expression between B6 mice and RORγt Tg mice, RORγt expression in Foxp3⁺ regulatory T cells were significantly higher in RORγt Tg mice than B6 mice. Most of Foxp3⁺ regulatory T cells expressed chemokine receptor 6, and which highly infiltrated in joints after the induction of CIA in RORγt Tg mice. Moreover, Foxp3⁺ regulatory T cells in RORγt Tg mice retain the expression of CD25, the suppressive function of effector CD4⁺ T cells in vitro, and IL-10 production as well as Foxp3⁺ regulatory T cells in B6 mice. In adoptive transfer of draining LN cells or CD4⁺cells from immunized mice, arthritis was significantly attenuated in recipient B6 mice transferred with cells from RORγt Tg mice. 

Conclusion: CIA was significantly suppressed in RORγt Tg mice, although IL-17 production and RORγt expression in CII reactive T cells was markedly higher than that of B6 mice. In vitro analyses and cell transfer experiments proposed the possibility that RORγt induced expression of CCR6 in Foxp3⁺ regulatory T cells, and these cells might regulate the development of CIA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/ror%ce%b3t-expressing-foxp3-regulatory-t-cells-regulates-the-development-of-autoimmune-arthritis-in-mice/